We have demonstrated (1) neoplastic transformation of SV40 T-antigen immortalized human epidermal keratinocytes by exposure of high linear energy transfer (LET) radiation. (2) detection of transforming genes from radiation-transformed human epidermal keratinocytes by a tumorigenicity assay. (3) demonstration of altered expression of extracellular matrix glycoproteins in malignant human papillomavirus type 6-transformed human keratinocytes. (4) demonstration of neoplastic transformation of immortalized human keratinocyte line (RHEK-1) by the HIV tat gene. and (5) immortalization of human tracheal gland epithelial cells by adenovirus 12-SV40 (Ad12-SV40) virus.